Comprehensive Analysis of Molecular Biologic Characteristics of Pancreatic Ductal Adenocarcinoma Concomitant with Intraductal Papillary Mucinous Neoplasm

Tsujimae, Masahiro; Masuda, Atsuhiro; Ikegawa, Takuya; Tanaka, Takeshi; Inoue, Jun; Toyama, Hirochika; Sofue, Keitaro; Uemura, Hiroji; Kohashi, Shinya; Inomata, Noriko; Nagao, Kae; Masuda, Shōgo; Abe, Shohei; Gonda, Masanori; Yamakawa, K.; Ashina, Shigeto; Yamada, Yasutaka; Tanaka, Shunta; Nakano, Ryota; Sakai, Arata; Kobayashi, Takashi; Shiomi, Hideyuki; Kanzawa, Maki; Itoh, Tomoo; Fukumoto, Takumi; Ueda, Yoshihide; Kodama, Yuzo

doi:10.1245/s10434-022-11704-z

Cited by 9 publications

(7 citation statements)

References 26 publications

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“…These differences in OS might suggest that PCN-PDAC shows different tumor biology as compared to PDAC not associated with PCN. However, a recent study did not find differences in the alteration frequency of the major driving genes between PDAC and IPMN-associated PDAC [ 20 ]. This hypothesis needs to be verified in larger prospective cohorts, in which more extensive molecular characterization such as whole genome sequencing, mRNA sequencing, and even methylation analysis is performed on both PCN-PDAC and PDAC not associated with PCN tumors, to create insight in possible differences in the tumor genome.…”

Section: Discussionmentioning

confidence: 99%

“…In contrast, a recently published retrospective single-center study by Holmberg et al reported that IPMN-PDAC was not associated with death in 513 patients (122 with IPMN-PDAC and 391 with other PDAC) [ 6 ]. Another single-center study also found no differences in overall and disease-free survival between PDAC concomitant with IPMN and other PDAC in 158 propensity score-matched subjects [ 20 ].…”

Section: Discussionmentioning

confidence: 99%

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Comparing Survival after Resection of Pancreatic Cancer with and without Pancreatic Cysts: Nationwide Registry-Based Study

Gorris

Huijgevoort

Sarasqueta

et al. 2022

Cancers

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Background: Outcome after resection of pancreatic ductal adenocarcinoma associated with pancreatic cystic neoplasms (PCN-PDAC) might differ from PDAC not associated with PCN. This nationwide, registry-based study aimed to compare the overall survival (OS) in these patients. Methods: Data from consecutive patients after pancreatic resection for PDAC between 2013 and 2018 were matched with the corresponding pathology reports. Primary outcome was OS for PCN-PDAC and PDAC including 1-year and 5-year OS. Cox regression analysis was used to correct for prognostic factors (e.g., pT-stage, pN-stage, and vascular invasion). Results: In total, 1994 patients underwent resection for PDAC including 233 (12%) with PCN-PDAC. Median estimated OS was better in patients with PCN-PDAC (34.5 months [95% CI 25.6 to 43.5]) as compared to PDAC not associated with PCN (18.2 months [95% CI 17.3 to 19.2]; hazard ratio 0.53 [95%CI 0.44–0.63]; p < 0.001). The difference in OS remained after correction for prognostic factors (adjusted hazard ratio 1.58 [95% CI 1.32−1.90]; p < 0.001). Conclusions: This nationwide registry-based study showed that 12% of resected PDAC were PCN-associated. Patients with PCN-PDAC had better OS as compared to PDAC not associated with PCN.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Comparing Survival after Resection of Pancreatic Cancer with and without Pancreatic Cysts: Nationwide Registry-Based Study

Gorris

Huijgevoort

Sarasqueta

et al. 2022

Cancers

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“…However, there have been no significant differences noted between pancreatic cancer alone and pancreatic cancer concomitant with IPMN in genetic alterations, the immune and fibrotic status of the tumor microenvironment and its prognosis. Additionally, the overall survival (OS) and disease-free survival (DFS) were not different between these groups of patients, and the coexistence of IPMNs does not worsen the prognosis of pancreatic cancer [ 18 ]. Determination of the molecular pathways involved in pancreatic cancer and IPMN is of great importance for an early diagnosis and further improvements of clinical outcomes [ 5 ].…”

Section: Genomic Profiling – Molecular Alterationsmentioning

confidence: 99%

“…Additionally, MRI assessment of cyst fluid together with other signs may predict the malignant transformation of IPMNs [58], assisted by three dimensional (3D)-MRCP [59] or 3T MRI [60]. It has been postulated that 18 F-Fluorodeoxyglucose ( 18 FDG)-PET is the best imaging tool for malignant cystic lesions [61]. A screening system using forward viewing radial EUS and MRI/MRCP for screening individuals with a family history of pancreatic cancer has been proposed [62].…”

Section:  Diagnosismentioning

confidence: 99%

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Modern aspects of the management of pancreatic intraductal papillary mucinous neoplasms: a narrative review

Pavlidis

Sapalidis²,

Pavlidis³

2022

Rom J Morphol Embryol

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Intraductal papillary mucinous neoplasms (IPMNs) account for approximately 35% of all cystic tumors in the pancreas and represent the largest subgroup. They are characterized by mucin production and intraductal papillary epithelium growth. IPMNs range from benign to malignant lesions. Biomarkers combined with 18F-Fluorodeoxyglucose–positron emission tomography (18FDG–PET) is the best diagnostic tool. The risk of malignant transformation for main-duct IPMNs is between 34–68% and for low-risk branch-duct (BD)-IPMNs it is 1.1%. Monitoring is crucial for determining the optimal time of surgical excision. Novel artificial intelligence combining clinical, tumor biomarkers, imaging and molecular genomics plays a determinant role in the evaluation of such lesions. The first diagnostic tool is multidetector helical computed tomography (MDHCT) or up-to-date magnetic resonance imaging (MRI). MRI detects malignancy by enhancing mural nodules ≥3 mm. Novel endosonographic interventional techniques have been added to the diagnostic armamentarium. Pancreatoscopy is feasible and effective but challenging for evaluating the diagnosis, invasiveness, and extent of IPMNs. Its findings may change the surgical approach. Pancreatic juice and duodenal fluid have been used recently for molecular biological analysis. The genes most frequently altered include Kirsten rat sarcoma viral proto-oncogene (KRAS), tumor protein p53 (TP53), cyclin-dependent kinase inhibitor 2A (CDKN2A), SMAD family member 4 (SMAD4), and guanine nucleotide-binding protein, alpha stimulating (GNAS). Despite the advances in diagnostic modalities, assessment of this premalignant lesion of pancreatic cancer, with its poor prognosis, is a challenging task. Pancreatectomy is the indicated approach for malignant or high-risk IPMNs with potent malignancy. Conservative management or enucleation for preserving the pancreas of low-risk BD-IPMNs is recommended, but long-term follow-up for recurrence is necessary. The management of IPMNs must be individualized based on preoperative high-risk stigmata and worrisome features.

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Histological variants of pancreatic ductal adenocarcinoma: a survival analysis

Bengtsson,

Andersson,

Ansari

2024

Langenbecks Arch Surg

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Purpose Pancreatic ductal adenocarcinoma (PDAC) can be classified into distinct histological subtypes based on the WHO nomenclature. The aim of this study was to compare the prognosis of conventional PDAC (cPDAC) against the other histological variants at the population level. Methods The Surveillance, Epidemiology and End Results (SEER) database was used to identify patients with microscopically confirmed PDAC. These patients were divided into 9 histological subgroups. Overall survival was assessed using the Kaplan-Meier method and Cox regression models stratified by tumor histology. Results A total of 159,548 patients with PDAC were identified, of whom 95.9% had cPDAC, followed by colloid carcinoma (CC) (2.6%), adenosquamous carcinoma (ASqC) (0.8%), signet ring cell carcinoma (SRCC) (0.5%), undifferentiated carcinoma (UC) (0.1%), undifferentiated carcinoma with osteoclast-like giant cells (UCOGC) (0.1%), hepatoid carcinoma (HC) (0.01%), medullary carcinoma of the pancreas (MCP) (0.006%) and pancreatic undifferentiated carcinoma with rhabdoid phenotype (PUCR) (0.003%). Kaplan-Meier curves showed that PUCR had the worst prognosis (median survival: 2 months; 5-year survival: 0%), while MCP had the best prognosis (median survival: 41 months; 5-year survival: 33.3%). In a multivariable Cox model, several histological subtypes (i.e. CC, ASqC, SRCC, UCOGC) were identified as independent predictors of overall survival when compared to cPDAC. Conclusion PDAC is a heterogenous disease and accurate identification of variant histology is important for risk stratification, as these variants may have different biological behavior.

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Comprehensive Analysis of Molecular Biologic Characteristics of Pancreatic Ductal Adenocarcinoma Concomitant with Intraductal Papillary Mucinous Neoplasm

Cited by 9 publications

References 26 publications

Comparing Survival after Resection of Pancreatic Cancer with and without Pancreatic Cysts: Nationwide Registry-Based Study

Comparing Survival after Resection of Pancreatic Cancer with and without Pancreatic Cysts: Nationwide Registry-Based Study

Modern aspects of the management of pancreatic intraductal papillary mucinous neoplasms: a narrative review

Histological variants of pancreatic ductal adenocarcinoma: a survival analysis

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